This application for a K23 Mentored Patient-Oriented Research Career Development Award includes a 5-year plan for training and research activities that will provide the skills and experience needed to achieve success as an independent investigator studying the role of the environment and epigenetic mechanisms in birth outcomes. The candidate has completed research and clinical fellowships that prepared her for an academic career studying perinatal social epidemiology and is currently a full-time faculty member in the Department of Neonatology at Beth Israel Deaconess Medical Center. The candidate is a core member of the Division of Newborn Medicine at Harvard Medical School serving as an Instructor in pediatrics, which is the standard entry level academic position at Harvard. This K23 award will provide her with the structure and support necessary to accomplish the following goals: (1) assess the role that arsenic plays in fetal growth;(2) assess the role arsenic plays in the DNA methylation of genes involved in fetal growth such as inflammatory cytokine genes and the glucocorticoid receptor gene, and explore whether arsenic affects fetal growth through such epigenetic mechanisms;(3) gain expertise in environmental toxicology and environmental epigenetic analyses;and (4) learn the administrative skills needed to manage a large cohort study so that transition to an independent research career running her own birth cohort is accomplished. The candidate's goal is to examine the role the toxic chemical environment plays in birth outcome disparities in the US. To achieve these goals, Dr. Burris has assembled a mentoring team comprised of a primary mentor, Robert Wright, MD MPH, Associate Professor of Pediatrics and Environmental Health who is an expert in pediatric environmental health and toxicology, and co-mentor Andrea Baccarelli, MD PhD, the Mark and Catherine Winkler Associate Professor of Environmental Epigenetics, who has expertise in epigenetic analyses. Although chemicals like arsenic are known to affect birth outcomes and known to affect DNA methylation, it remains unknown whether DNA methylation mediates arsenic-birth weight associations. The study proposed is designed to test the hypothesis that arsenic impairs fetal growth, that arsenic causes alterations in the DNA methylation of inflammatory cytokine genes and the glucocorticoid receptor gene. The candidate will explore whether DNA methylation disturbances mediate arsenic-birth weight associations. These analyses will be performed within a previously established, currently funded cohort in Mexico City (ELEMENT) directed by Dr. Wright. The candidate will use the abundant resources available at Beth Israel Deaconess Medical Center, the Harvard Catalyst (Clinical and Translational Science Center) and the Harvard School of Public Health to obtain the training and coursework necessary to supplement the practical training attained through these analyses to become an independent investigator with a research program studying the environmental impact on birth outcome disparities. Public Health Relevance: Poor fetal growth is associated with short-term perinatal morbidity and mortality as well as long-term poor health later in life. Arsenic exposure during pregnancy has been shown to potentially inhibit fetal growth in animals and to be associated with low birth weights in humans. Understanding the biology of arsenic toxicity and its effect on fetal growth may ultimately spurn tighter environmental regulation policies, trigger clean-up efforts and allow for targeted therapies during pregnancies affected by high arsenic exposure.

Public Health Relevance

Poor fetal growth is associated with short-term perinatal morbidity and mortality as well as long-term poor health later in life. Arsenic exposure during pregnancy has been shown to potentially inhibit fetal growth in animals and to be associated with low birth weights in humans. Understanding the biology of arsenic toxicity and its effect on fetal growth may ultimately spurn tighter environmental regulation policies, trigger clean-up efforts and allow for targeted therapies during pregnancies affected by high arsenic exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23ES022242-02
Application #
8575336
Study Section
Special Emphasis Panel (ZES1-JAB-J (K9))
Program Officer
Shreffler, Carol K
Project Start
2012-12-01
Project End
2017-10-31
Budget Start
2013-11-01
Budget End
2014-10-31
Support Year
2
Fiscal Year
2014
Total Cost
$157,476
Indirect Cost
$10,882
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Yamamoto, A; McCormick, M C; Burris, H H (2015) Disparities in antidepressant use in pregnancy. J Perinatol 35:246-51
Burris, H H; Thomas, A; Zera, C A et al. (2015) Prenatal vitamin use and vitamin D status during pregnancy, differences by race and overweight status. J Perinatol 35:241-5
Burris, Heather H; Camargo Jr, Carlos A (2014) Time for large randomised trials of vitamin D for women with gestational diabetes mellitus to improve perinatal health outcomes. Diabetologia 57:1746-8
Burris, Heather H; Baccarelli, Andrea A; Motta, Valeria et al. (2014) Association between length of gestation and cervical DNA methylation of PTGER2 and LINE 1-HS. Epigenetics 9:1083-91
Burris, Heather H; Rifas-Shiman, Sheryl L; Huh, Susanna Y et al. (2014) Vitamin D status and hypertensive disorders in pregnancy. Ann Epidemiol 24:399-403.e1
Burris, Heather H; Camargo Jr, Carlos A (2014) Vitamin D and gestational diabetes mellitus. Curr Diab Rep 14:451
Burris, Heather H; Baccarelli, Andrea A (2014) Environmental epigenetics: from novelty to scientific discipline. J Appl Toxicol 34:113-6
Braun, Joseph M; Wright, Rosalind J; Just, Allan C et al. (2014) Relationships between lead biomarkers and diurnal salivary cortisol indices in pregnant women from Mexico City: a cross-sectional study. Environ Health 13:50
Burris, Heather H; Van Marter, Linda J; McElrath, Thomas F et al. (2014) Vitamin D status among preterm and full-term infants at birth. Pediatr Res 75:75-80
Burris, Heather H; Braun, Joe M; Byun, Hyang-Min et al. (2013) Association between birth weight and DNA methylation of IGF2, glucocorticoid receptor and repetitive elements LINE-1 and Alu. Epigenomics 5:271-81